Nitroxide radicals prevent metal-aggravated reperfusion injury in isolated rat heart.
The effects of Cu(II) and the stable nitroxide radical 4-OH-2, 2, 6, 6-tetramethyl-piperidine-1-oxyl (TPL) on reperfusion injury following global myocardial ischemia have been studied using the isolated rat heart model in the Langendorff configuration. Hearts were equilibrated with Krebs-Henseleit buffer (KH-buffer) for 10 min and subjected to 18 min of normothermic global ischemia. After 20 min reperfusion, hemodynamic parameters recovered as follows: ventricular developed pressure (77%), dP/dt (71%) and -dP/dt (80%), heart rate (91%), and work index (70%). End-diastolic pressure was 16 mm Hg. When 10 microM Cu-nitrilotriacetate or Cu-(histidine)2 was included in the perfusate before, during, and following ischemia, the heart injury was more extensive and the work index only recovered to 17% of the preischemic value. The inclusion of 100 microM TPL during reperfusion abolished the copper-induced sensitization. In the absence of copper, TPL did not provide any protection against ischemia-reperfusion damage to the heart. The inclusion of 100 microM 1,4-dihydroxy-2,2,6,6-tetramethylpiperidine (TPL-H) during reperfusion, partially abolished the copper-induced sensitization. Since conversion between TPL and TPL-H takes place, the fact that both forms provide protection can increase their protective efficacy.
Zeltcer
G
G
Department of Cellular Biochemistry, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Berenshtein
E
E
Samuni
A
A
Chevion
M
M
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D003300:Copper / Q000037:antagonists & inhibitors*; D003497:Cyclic N-Oxides / Q000378:metabolism*; D019811:Hydroxylamine / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000378:metabolism*; D009589:Nitrogen Oxides / Q000378:metabolism* / Q000494:pharmacology; D010710:Phosphates / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013113:Spin Labels
C110289:4-hydroxy-2,2,6,6--tetramethylpiperidine-1-N-hydroxyl; D000975:Antioxidants; D003497:Cyclic N-Oxides; D009589:Nitrogen Oxides; D010710:Phosphates; D010880:Piperidines; D013113:Spin Labels; D019811:Hydroxylamine; D003300:Copper; C039900:nitroxyl; C001803:tempol